Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Toxicokinetic Assessment
Adequacy of study:
key study
Study period:
February 28, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxicokinetic Assessment by a certified toxicologist.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008
Reference Type:
other: amendment
Title:
Unnamed
Year:
2011

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Test guideline
Qualifier:
according to
Guideline:
other: Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, May 2008.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Radia 7838
- Description: Yellow to amber liquid

Results and discussion

Main ADME results
Type:
absorption
Results:
For risk assessment purposes, the oral and dermal absorption is set at 50% and the inhalation absorption is set at 100%

Any other information on results incl. tables

This substance is a polyester. The toxicokinetic assessment is based on the physical/chemical properties as determined for the test
substance and it is anticipated that these properties are representative for all constituents in this substance. The
different components in the test substance however are considered to have different lipophilicity. This is
represented by the octanol/water partition coefficient which is given as a range (< 0.3 - > 6.5).

The water solubility is very low (<1 mg/L). Since in general a substance needs to be dissolved before it can be taken up
from the gastro-intestinal tract, it is unlikely that the test substance will show a high systemic exposure after oral
administration. As ionized substances do not easily pass the GI wall, the presence of free hydroxyl groups in the
molecule will further impair the absorption. It is not to be expected that the not clearly defined molecular weight
(approx. 400) will further lower the passage through biological membranes. As its lipophilic character (logPow <
0.3 - > 6.5) is not clearly defined, no conclusions can be drawn based on this parameter and hence on how this might
influence passive diffusion and on the relevance of micellular solubilization. For risk assessment purposes the
oral absorption of the test substance is set at 50%. The results of the toxicity studies do not provide reasons to
deviate from this proposed oral absorption factor.

No significant cleavage of the ester bound(s) is to be expected in the gastro-intestinal tract, due to the limited
water solubility.  In the case absorption of the test substance occurs, cleavage of the ester bonds and
conjugation is to be expected. The test substance, the resulting metabolites and conjugation products will be
excreted via feces (high molecular substances) or via urine (low molecular substances).

The low vapour pressure (< 1.47 x 10^-3 Pa) indicates that the availability of the substance for inhalation will be
limited. However, once present in the respiratory tract, the low water solubility (<1 mg/L) indicates a potential for
accumulation, while based on its undefined lipophilic character (logPow < 0.3 - > 6.5) the potential for
absorption directly across the respiratory tract epithelium cannot be assessed. For risk assessment purposes the
inhalation absorption of the test substance is set at 100% as a worst case assumption.

The low water solubility (<1 mg/L) does not facilitate dermal absorption. As its lipophilic character is not
clearly defined, but approx. 80% of the substance has a logPow of >4 and the molecular weigth is approx. 400, the criterion for 100% dermal absorption (MW < 500 and/or -1 < log Po/w < 4) is partially met. It is generally accepted however that dermal absorption is lower compared to oral absorption. Therefore, for risk assessment purposes a dermal absorption value of 50% is considered appropriate.
Based on the present available data, no additional conclusions can be drawn on the metabolism and excretion
after dermal and inhalatory absorption.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Main ADME results: The absorption factors for risk assessment purposes have been set by a certified toxicologist: absorption oral 50%, absorption dermal 50% and absorption inhalation 100%
For risk assessment purposes:
Absorption oral = 50%
Absorption dermal = 50%
Absorption inhalation = 100%